POS1047 RNA-SEQUENCING OF CLASSICAL MONOCYTES FROM RHEUMATOID ARTHRITIS PATIENTS WITH AND WITHOUT BONE EROSION
Authors: L. Peixoto Sales, B. Hounkpe, M. Perez, V. Caparbo, D. S. Domiciano, E. Borba, C. Figueiredo, R. M. Pereira
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by systemic and localized bone impairment. Bone erosions, the hallmark lesions of RA, are an important predictor of disability, disease severity, and mortality. The arising of bone erosions is triggered by chronic inflammation, mediated mainly by immune cells. Under inflammatory conditions, classical (CD14++CD16-) monocytes are the main source of osteoclasts precursors, the accountable cells responsible for bone resorption process. Although previous transcriptomic studies have shown that CD14++CD16- monocytes have high expression of genes involved in inflammation and in extracellular matrix degradation process, there is no data regarding the impact of CD14++CD16- monocytes on bone destruction in RA. <h3>Objectives</h3> To analyze CD14++CD16- monocytes transcriptomic profile from RA patients presenting bone erosions evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT), comparing with RA patients without bone erosions and healthy controls. <h3>Methods</h3> Thirty-nine premenopausal RA women were included in this study. Based on bone erosion identification on metacarpophalangeal and proximal interphalangeal joints of the dominant hand assessed by HR-pQCT, RA patients were classified into two groups according to the presence or absence of bone erosions. Twenty age- and body mass index-matched healthy subjects were enrolled in the control group. CD14++CD16- monocytes were indirectly isolated using the CD16 MicroBeads, and RNA-Sequencing was performed. Transcriptome analysis of CD14++CD16- monocytes from control group were used to account for background expression. The differentially expressed genes (DEGs) were identified and the analysis of the biological pathways was performed using bioinformatics tools. <h3>Results</h3> RNA-seq analysis revealed 1140 DEGs in RA patients with erosion, of which 89 were up-regulated and 1051 down-regulated compared to the group of patients without erosion. A top ranked genes suggested that the up-regulated genes were highly associated with immune response and cytokine activation. Interestingly, the down-regulated genes were associated with bone formation and wound healing (Table 1). Enriched pathways in patients with erosion were associated with substantial activation of immunity and inflammation. Pathways associated with osteoblast differentiation and the regulation of Wnt signaling were less activated in RA patients with erosion. Interesting, while the activity of immune pathways was positively correlated with the number of bone erosions, a negative correlation was observed between the number of erosions with osteoblast differentiation and regulation of cell matrix adhesion. <h3>Conclusion</h3> These findings suggest that increasing of immuno-inflammatory activation and impairment of bone formation processes might potentially be a key driver of bone erosion in RA pathogenesis. <h3>References</h3> [1] Rana AK et al., Monocytes in rheumatoid arthritis: Circulating precursors of macrophages and osteoclasts and, their heterogeneity and plasticity role in RA pathogenesis. Int Immunopharmacol 2018; 65: 348–59. [2] Schett G et al., Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment. Nat Rev Rheumatol 2012; 8: 656–64. <h3>Acknowledgements</h3> Our acknowledgement to Prof. Dr Rosa MR Pereira (in memorian) who was responsible for the project starting. <h3>Disclosure of Interests</h3> None Declared.